Thyroid hormone receptor binding to DNA and T3-dependent transcriptional activation are inhibited by uremic toxins

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Autor(es): dc.creatorSantos, Guilherme M.-
Autor(es): dc.creatorPantoja, Carlos J.-
Autor(es): dc.creatorSilva, Aluízio Costa e-
Autor(es): dc.creatorRodrigues, Maria Cristina Soares-
Autor(es): dc.creatorRibeiro, Ralff Carvalho Justiniano-
Autor(es): dc.creatorSimeoni, Luiz Alberto-
Autor(es): dc.creatorLomri, Noureddine-
Autor(es): dc.creatorNeves, Francisco de Assis Rocha-
Data de aceite: dc.date.accessioned2024-10-23T16:21:02Z-
Data de disponibilização: dc.date.available2024-10-23T16:21:02Z-
Data de envio: dc.date.issued2009-09-18-
Data de envio: dc.date.issued2009-09-18-
Data de envio: dc.date.issued2005-09-18-
Fonte completa do material: dc.identifierhttp://repositorio.unb.br/handle/10482/1705-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/906168-
Descrição: dc.descriptionBackground: There is a substantial clinical overlap between chronic renal failure (CRF) and hypothyroidism, suggesting the presence of hypothyroidism in uremic patients. Although CRF patients have low T3 and T4 levels with normal thyroid-stimulating hormone (TSH), they show a higher prevalence of goiter and evidence for blunted tissue responsiveness to T3 action. However, there are no studies examining whether thyroid hormone receptors (TRs) play a role in thyroid hormone dysfunction in CRF patients. To evaluate the effects of an uremic environment on TR function, we investigated the effect of uremic plasma on TRβ1 binding to DNA as heterodimers with the retinoid X receptor alpha (RXRα) and on T3-dependent transcriptional activity. Results: We demonstrated that uremic plasma collected prior to hemodialysis (Pre-HD) significantly reduced TRβ1-RXRα binding to DNA. Such inhibition was also observed with a vitamin D receptor (VDR) but not with a peroxisome proliferator-activated receptor gamma (PPARγ). A cell-based assay confirmed this effect where uremic pre-HD ultrafiltrate inhibited the transcriptional activation induced by T3 in U937 cells. In both cases, the inhibitory effects were reversed when the uremic plasma and the uremic ultrafiltrate were collected and used after hemodialysis (Post-HD). Conclusion: These results suggest that dialyzable toxins in uremic plasma selectively block the binding of TRβ1-RXRα to DNA and impair T3 transcriptional activity. These findings may explain some features of hypothyroidism and thyroid hormone resistance observed in CRF patients.-
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Direitos: dc.rightsAcesso Aberto-
Direitos: dc.rights© 2005 Santos et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Fonte: http://www.nuclear-receptor.com/content/3/1/1#IDAZEKPK.-
Palavras-chave: dc.subjectThyroid hormone (TSH)-
Palavras-chave: dc.subjectDNA-
Palavras-chave: dc.subjectUremic toxins-
Palavras-chave: dc.subjectT3-dependent-
Título: dc.titleThyroid hormone receptor binding to DNA and T3-dependent transcriptional activation are inhibited by uremic toxins-
Tipo de arquivo: dc.typelivro digital-
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